1bht
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NK1 FRAGMENT OF HUMAN HEPATOCYTE GROWTH FACTOR
OverviewOverview
BACKGROUND: Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, and has also been implicated as an epithelial morphogen in tumor invasion., HGF activates its specific cellular receptor, c-met, through an, aggregation mechanism potentiated by heparan sulfate glycosaminoglycans., HGF consists of an N-terminal (N) domain, four kringle domains (the first, of which carries receptor-binding determinants), and an inactive, serine-protease-like domain. NK1, a naturally occurring fragment of HGF, acts as an antagonist of HGF in the absence of heparin. RESULTS: The N, domain of NK1 consists of a central five-stranded antiparallel beta sheet, flanked by an alpha helix and a two-stranded beta ribbon. The overall N, domain structure in the context of the NK1 fragment is similar to the, structure of the isolated domain; two lysines and an arginine residue, coordinate a bound sulfate ion. The NK1 kringle domain is homologous to, kringle 4 from plasminogen, except that the lysine-binding pocket is, altered by the insertion of a glycine residue. Here, a HEPES molecule is, bound in the pocket. The asymmetric unit of the crystal contains a, 'head-to-tail' NK1 dimer. We use this dimer to propose a model of the NK2, fragment of HGF. CONCLUSIONS: A cluster of exposed lysine and arginine, residues in or near the hairpin-loop region of the N domain might form, part of the NK1 heparin-binding site. In our NK2 model, both kringle, domains pack loosely against the N domain, and a long, positively charged, groove lines the interface. This groove might be involved in, glycosaminoglycan binding. The HGF receptor-binding determinants are, clustered near the binding pocket of the first kringle domain, opposite, the N domain.
DiseaseDisease
Known diseases associated with this structure: Fibromatosis, gingival OMIM:[182530], Noonan syndrome 4 OMIM:[182530]
About this StructureAbout this Structure
1BHT is a Single protein structure of sequence from Homo sapiens with SO4 and EPE as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution., Ultsch M, Lokker NA, Godowski PJ, de Vos AM, Structure. 1998 Nov 15;6(11):1383-93. PMID:9817840
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